Timing of Extinction Relative to Acquisition: A Parametric Analysis of Fear Extinction in Humans

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Behavioral Neuroscience (Impact Factor: 2.73). 11/2008; 122(5):1016-30. DOI: 10.1037/a0012604
Source: PubMed


Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans.

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Available from: Bram Vervliet
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    • "While in some studies immediate extinction produced less return of fear compared to delayed extinction (Myers et al., 2006), this was not replicated in other studies (Archbold et al., 2010;). There is even evidence that immediate extinction produces poorer long-term fear reduction and more return of fear (Maren and Chang, 2006;Norrholm et al., 2008;Huff et al., 2009), i.e., an ''immediate extinction deficit'' (for a review, seeMaren, 2014). Importantly, stress, stress-response mediators and sex hormones may influence each of the phases of extinction learning and memory formation differently. "
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    ABSTRACT: Fear acquisition and extinction are valid models for the etiology and treatment of anxiety, trauma- and stressor-related disorders. These disorders are assumed to involve aversive learning under acute and/or chronic stress. Importantly, fear conditioning and stress share common neuronal circuits. The stress response involves multiple changes interacting in a time-dependent manner: (a) the fast first-wave stress response (with central actions of noradrenaline, dopamine, serotonin, corticotropin-releasing hormone, plus increased sympathetic tone and peripheral catecholamine release) and (b) the second-wave stress response (with peripheral release of glucocorticoids after activation of the hypothalamus-pituitary-adrenocortical axis). Control of fear during extinction is also sensitive to these stress-response mediators. In the present review, we will thus examine current animal and human data, addressing the role of stress and single stress-response mediators for successful acquisition, consolidation and recall of fear extinction. We report studies using pharmacological manipulations targeting a number of stress-related neurotransmitters and neuromodulators (monoamines, opioids, endocannabinoids, neuropeptide Y, oxytocin, glucocorticoids) and behavioral stress induction. As anxiety, trauma- and stressor-related disorders are more common in women, recent research focuses on female sex hormones and identifies a potential role for estradiol in fear extinction. We will thus summarize animal and human data on the role of estradiol and explore possible interactions with stress or stress-response mediators in extinction. This also aims at identifying time-windows of enhanced (or reduced) sensitivity for fear extinction, and thus also for successful exposure therapy.
    Full-text · Article · Jan 2016 · Frontiers in Behavioral Neuroscience
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    • "Interestingly, the observation of nondifferential (generalized ) ROF is also evident in other ROF phenomena such as renewal (for review, see Vervliet et al. 2013a) and spontaneous recovery (Norrholm et al. 2008). Further complicating matters, often a mixture of differential, generalized, and no reinstatement effects in different dependent measures is reported within one study (see Table 1 for a detailed summary of the results of human studies). "

    Full-text · Dataset · Jan 2015
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    • "Although some studies have shown that spontaneous recovery can be modified by the delay intervals between acquisition and extinction testing (e.g. Huff, Hernandez, Blanding, & LaBar, 2009; Norrholm et al., 2008; Schiller et al., 2008), it is unknown whether multiple-context extinction has any effect on spontaneous fear recovery. Spontaneous recovery is typically tested in the extinction context following a delay (i.e. "
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    ABSTRACT: Although conditioned fear can be effectively extinguished by unreinforced exposure to a threat cue, fear responses tend to return when the cue is encountered some time after extinction (spontaneous recovery), in a novel environment (renewal), or following presentation of an aversive stimulus (reinstatement). As extinction represents a context-dependent form of new learning, one possible strategy to circumvent the return of fear is to conduct extinction across several environments. Here, we tested the effectiveness of multiple context extinction in a two-day fear conditioning experiment using 3-D virtual reality technology to create immersive, ecologically-valid context changes. Fear-potentiated startle served as the dependent measure. All three experimental groups initially acquired fear in a single context. A multiple extinction group then underwent extinction in three contexts, while a second group underwent extinction in the acquisition context and a third group underwent extinction in a single different context. All groups returned 24 hours later to test for return of fear in the extinction context (spontaneous recovery) and a novel context (renewal and reinstatement/test). Extinction in multiple contexts attenuated reinstatement of fear but did not reduce spontaneous recovery. Results from fear renewal were tendential. Our findings suggest that multi-context extinction can reduce fear relapse following an aversive event – an event that often induces return of fear in real-world settings -- and provides empirical support for conducting exposure-based clinical treatments across a variety of environments.
    Full-text · Article · Sep 2014 · Neurobiology of Learning and Memory
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